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Difference between revisions of "Course:Introduction to Neuropathology"
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Course:Introduction to Neuropathology (view source)
Revision as of 09:00, 8 October 2015
, 09:00, 8 October 2015→Molecular neuropathology: Myopathology (Source: en. wikipedia.org + wikimedia commons)
Jensflorian (talk | contribs) (day 2 molecular neurooncology) |
Jensflorian (talk | contribs) (→Molecular neuropathology: Myopathology (Source: en. wikipedia.org + wikimedia commons)) |
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Because [[IDH-1]] and IDH-2 mutations are found in up to 80% of [[astrocytoma]]s and [[oligodendroglioma]], IDH-1 R132H (which detects only the R132H substitution <ref name=pmid19798509>{{Cite journal | last1 = Capper | first1 = D. | last2 = Zentgraf | first2 = H. | last3 = Balss | first3 = J. | last4 = Hartmann | first4 = C. | last5 = von Deimling | first5 = A. | title = Monoclonal antibody specific for IDH1 R132H mutation. | journal = Acta Neuropathol | volume = 118 | issue = 5 | pages = 599-601 | month = Nov | year = 2009 | doi = 10.1007/s00401-009-0595-z | PMID = 19798509 }}</ref>) stained negative cases are sequenced for other rare mutations that include IDH1 R132C or IDH2 R172K among others. These mutations are not only useful in differential diagnosis of brain tumours but also prognostic, because tumours carrying a IDH-1 or IDH-2 mutation usually show a more favourable course than their wild-type counterparts <ref name=pmid21088844>{{Cite journal | last1 = Hartmann | first1 = C. | last2 = Hentschel | first2 = B. | last3 = Wick | first3 = W. | last4 = Capper | first4 = D. | last5 = Felsberg | first5 = J. | last6 = Simon | first6 = M. | last7 = Westphal | first7 = M. | last8 = Schackert | first8 = G. | last9 = Meyermann | first9 = R. | title = Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. | journal = Acta Neuropathol | volume = 120 | issue = 6 | pages = 707-18 | month = Dec | year = 2010 | doi = 10.1007/s00401-010-0781-z | PMID = 21088844 }}</ref>. | Because [[IDH-1]] and IDH-2 mutations are found in up to 80% of [[astrocytoma]]s and [[oligodendroglioma]], IDH-1 R132H (which detects only the R132H substitution <ref name=pmid19798509>{{Cite journal | last1 = Capper | first1 = D. | last2 = Zentgraf | first2 = H. | last3 = Balss | first3 = J. | last4 = Hartmann | first4 = C. | last5 = von Deimling | first5 = A. | title = Monoclonal antibody specific for IDH1 R132H mutation. | journal = Acta Neuropathol | volume = 118 | issue = 5 | pages = 599-601 | month = Nov | year = 2009 | doi = 10.1007/s00401-009-0595-z | PMID = 19798509 }}</ref>) stained negative cases are sequenced for other rare mutations that include IDH1 R132C or IDH2 R172K among others. These mutations are not only useful in differential diagnosis of brain tumours but also prognostic, because tumours carrying a IDH-1 or IDH-2 mutation usually show a more favourable course than their wild-type counterparts <ref name=pmid21088844>{{Cite journal | last1 = Hartmann | first1 = C. | last2 = Hentschel | first2 = B. | last3 = Wick | first3 = W. | last4 = Capper | first4 = D. | last5 = Felsberg | first5 = J. | last6 = Simon | first6 = M. | last7 = Westphal | first7 = M. | last8 = Schackert | first8 = G. | last9 = Meyermann | first9 = R. | title = Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. | journal = Acta Neuropathol | volume = 120 | issue = 6 | pages = 707-18 | month = Dec | year = 2010 | doi = 10.1007/s00401-010-0781-z | PMID = 21088844 }}</ref>. | ||
[[Oligodendroglioma]]s show a more favourable course and therfore are treated differently than [[astrocytoma]]s. A clear separation of these two entities is important, because [[H&E]] morphology is not always convincing. Succesful treatment depends on allelic losses on chromosomal arms 1p and 19q in oligodendroglioma that can be obtained by copy-number analysis or microsatellite PCR. By combining LOH (loss of heterozygosity) 1p/19q and [[ATRX]] status it is also possible to place the mixed [[oligoastrocytoma]]s into the astrocytoma or oligodendroglioma group. | [[Oligodendroglioma]]s show a more favourable course and therfore are treated differently than [[astrocytoma]]s. A clear separation of these two entities is important, because [[H&E]] morphology is not always convincing. Succesful treatment depends on allelic losses on chromosomal arms 1p and 19q in oligodendroglioma that can be obtained by copy-number analysis or microsatellite PCR. By combining LOH (loss of heterozygosity) 1p/19q and [[ATRX]] status it is also possible to place the mixed [[oligoastrocytoma]]s into the astrocytoma or oligodendroglioma group. | ||
===Day 1=== | |||
====Immunofluorescence==== | |||
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope (usually a confocal microscope). This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows visualisation of the distribution of the target molecule through the sample. The typical approach uses a unlabeled first (primary) antibody that specifically binds the target molecule, and the secondary antibody, which carries the fluorophore, recognises the primary antibody and binds to it. Advantages of immunofluorescence are the usually better resolution of the signals compared with standard light-microscope stains and the possibility to combine antibodies of different species to target two or more epitopes with different fluorophores. These different signals can be merged into a single image. | |||
<gallery> | |||
File:VIMENTIN.jpg | Immunofluorescence staining for vimentin in human epithelial cells (green). | |||
File:Neuron in tissue culture.jpg | Combined immunofluoerescence to visualize Neurofilament (green) and alpha-internexin (red). | |||
</gallery> | |||
====Myopathology==== | |||
The skeletal muscle is anchored by tendons (or by aponeuroses at a few places) to bone and is used to effect skeletal movement such as locomotion and to maintain posture. Striated or skeletal muscle only contracts voluntarily, upon influence of the central nervous system.Skeletal muscle is further divided into several subtypes: | |||
* Type I, slow oxidative, slow twitch, or "red" muscle is dense with capillaries and is rich in mitochondria and myoglobin, giving the muscle tissue its characteristic red color. It can carry more oxygen and sustain aerobic activity. | |||
* Type II, fast twitch muscle, has three major kinds that are, in order of increasing contractile speed. | |||
Muscle biopsies are performed to obtain a specific diagnosis in persisting weakness or muscle pain. | |||
<gallery> | |||
File:1007 Muscle Fibes (large).jpg | Structure of myofibers. | |||
File:Denervation atrophy - high mag.jpg | Cross section of skeletal muscle (HE stain). The variation in size is due to loss of innervation (neurogenic atrophy). | |||
File:DM2 Histopathology.jpg | Slow myosin staining in muscle cross section highlighting type 1 fibers (brown). | |||
File:Polymyositis HE.jpg | Inflammatory cells in muscle fibers allow the diagnosis of myositis. | |||
File:Pompe vacuoles.jpg | Defects in muscle enzymes result in abnormal storage - here vacuoles in acid maltase deficiency. | |||
File:LGMD2D alpha sarcoglycan.jpg | Inherited diseases often affect elementar structural proteins, as seen here with alpha-sarcoglycan deficiency in limb-girdle musculary dystrophy (B). | |||
</gallery> | |||
==References== | ==References== | ||